The purpose of this FOA is to support projects
investigating the interplay between molecular regulation of brain energy
utilization and brain and/or behavioral changes resulting from chronic
exposure to abused substances.

Key Dates

Posted Date

May 3, 2013

Open Date (Earliest Submission Date)

July 15, 2013

Letter of Intent Due Date(s)

July 15, 2013

Application Due Date(s)

August 15, 2013, by 5:00 PM local time of applicant
organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the submission
process by the due date.

AIDS Application Due Date(s)

August 15, 2013, by 5:00 PM local time of applicant
organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

Scientific Merit Review

October/November 2013

Advisory Council Review

January 2014

Earliest Start Date

April 2014

Expiration Date

August 16, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all application
instructions in the Application Guide as well as any program-specific
instructions noted in Section IV. When
the program-specific instructions deviate from those in the Application Guide,
follow the program-specific instructions. Applications that do not
comply with these instructions may be delayed or not accepted for review.

Brain
energetics. Although the human brain is approximately 2% of
total body mass, 25% of the glucose used by the body is consumed by brain
functions (Belanger, et al. 2011 Cell Metabolism 14:724-738). The detailed
molecular mechanisms by which the brain utilizes glucose are still not
completely understood, but there is a growing body of evidence that suggests a
complex reciprocal exchange of metabolic intermediates between neurons and
glia. In broad strokes, astrocytes take up glucose from the blood and supply
the bulk of their energy needs through non-oxidative metabolism of glucose,
resulting in the production of significant quantities of lactate. Neurons, on
the other hand, do not directly metabolize significant amounts of glucose, but
rather take up lactate that is generated and released by astrocytes. This
lactate is used by neurons to generate ATP aerobically via the tricarboxylic
acid (TCA) cycle in the mitochondria.

Energy regulation plays an important role in several
fundamental brain processes. For example, lactate transport between astrocytes
and neurons has been shown to be required for long-term memory formation
(Suzuki et al. 2011 Cell 144:810-823). Recent studies have shown that
mitochondrial biogenesis plays a role in dendritic spine formation and
maintenance (Cheng et al. 2012 Nat. Commun. 3:1250). Brain energy utilization
influences neuronal/glial cycling of glutamine and the neurotransmitter
glutamate, which may impact glutamate signaling. Dysregulation of brain energy
utilization can also be associated with certain disease states. For example,
mitochondrial dysfunction can lead to increasingly uncoupled aerobic metabolism
resulting in the generation of large quantities of reactive oxygen species
(ROS) which have been implicated in apoptosis and neurodegenerative diseases
(Federico, et al. 2012 J. Neurol. Sci. 322:254-262). Additionally, some common
brain imaging approaches depend on the disparities between brain metabolism and
oxygen consumption to measure energetic changes. For example, functional
magnetic resonance imaging fMRI can measure blood oxygen levels using BOLD,
while positron emission tomography (PET) can measure changes in brain glucose
levels using fluorodeoxyglucose (Raichle and Mintun 2006 Ann. Rev. Neurosci.
29:449-476). Despite the extraordinary importance of brain energy homeostasis,
there is limited research exploring the molecular mechanisms regulating the
intracellular pathways involved as well as the intercellular communication
between the neurons and glia that mediate these processes.

Environmental
exposures and brain energy utilization. Another issue to
consider is the effect of acute and chronic environmental exposures on brain
energy utilization. For example, although the influence of diet on brain
energy utilization is not well characterized, a high-fat, low-carbohydrate,
adequate-protein ketogenic diet has been used successfully to treat some cases
of pediatric epilepsy (Vining et al.1998 Arch. Neurol. 55:1433-1437). It is
thought that this diet dramatically alters the metabolic biochemistry within
the brain, switching from a glucose-based to a ketone-based metabolism. There
is also evidence that this ketogenic diet may be neuroprotective and may reduce
pain and inflammation (Lutas and Yellen 2013 Trends Neurosci. 36: 32-40;
Ruskin et al. 2009 PLoS One 4(12):e8349).

The extent to which non-dietary metabolic modifiers may
influence brain energy regulation and function is also not well understood.
For example, exercise, diabetes status, or diabetes treatments could have
important impacts on brain energy regulation and processes such as motor
control and cognitive functioning (Matsui et al. 2012 J. Physiol. 590:
607-616). Furthermore, environmental stimuli such as food and light can entrain
our circadian clocks, suggesting an intimate linkage between the clock and
metabolic regulation. Circadian clocks are involved in regulation of our
sleep-wake cycle and there is evidence that brain metabolism differs during the
course of these cycles (e.g. Dash et al. 2012 Sleep 35:909-919). Epigenetic
regulation appears to be an important mediator between the clock and metabolism
(Masri and Sassone-Corsi 2013 Nat. Rev. Neuro. 14:69-75). In addition,
astrocytes can release ATP into the extracellular space where it is hydrolyzed
to the inhibitory neurotransmitter adenosine, which plays an important role in
the regulation of neuronal excitability, arousal and sleep (Schmitt et al. 2012
J. Neurosci. 32(13):4417-4425).

The purpose of this FOA is to support projects investigating
the interplay between molecular regulation of brain energy utilization and
brain and/or behavioral changes resulting from chronic exposure to abused
substances. Applicants MUST focus their applications on one or more
substances of abuse (e.g. nicotine, stimulants, opioids, cannabinoids,
inhalants, abused prescription medicines, psychedelic drugs, caffeine, etc.).
Studies investigating chronic, rather than acute, exposure to abused substances
and studies involving drug withdrawal, reinstatement, or related paradigms are
of particular interest. Investigators with limited experience in substance
abuse research are encouraged to collaborate with researchers that have
substance abuse expertise. Applications submitted to this FOA also MUST have a
primary focus on molecular mechanisms regulating brain energy utilization. As
a consequence, it is anticipated that most applicants will choose to exploit biological
systems in which brain material is available for molecular analyses.
Researchers with interesting observations on brain energy utilization in human
subjects may wish to collaborate with researchers with access to the
appropriate tissues to investigate their hypotheses at the molecular level. To
avoid submitting an application that is not responsive to this FOA, applicants
should carefully review the submission requirements for this FOA in Section IV.2 and ensure that they have included all
of the components needed in the Research Plan. Applicants are encouraged to
contact NIDA program staff (see Scientific/Research
Contact) for additional guidance on scientific priorities and application
responsiveness.

This FOA utilizes the R01 mechanism and is appropriate for
projects with preliminary data supporting the proposed specific aims.
Exploratory high risk/high impact studies that lack significant preliminary
data should use the R21 mechanism through the companion FOA (RFA-DA-14-006).
In all cases the proposed budget should be commensurate with the research
proposed.

Some potential research questions of NIDA interest might
include:

What molecular processes regulate brain energy utilization? How
do these regulatory processes impact the functions of neurons, or glia, or
their interactions? How do these energy regulatory processes synergize with or
oppose molecular events that occur in response to exposure to substances of
abuse?

How do drugs of abuse affect brain energy substrate preference
over time? Are alternative substrates of energy metabolism utilized due to
substance use? To what extent does the brain rely on circulating glucose or
glucose metabolites that cross the blood brain barrier as opposed to
metabolites produced in the brain? Is brain energy substrate preference
affected by co-occurring brain dysfunctions, acute or chronic pain, or by
salient visual cues? What molecular mechanisms regulate these processes?

What transcription factors or epigenetic regulatory processes
influence regulation of brain energy utilization? Do substances of abuse
impact these same processes?

Are there differences in molecular regulation of energy
utilization in different brain regions (e.g. reward circuitry versus executive
circuitry) with and without exposure to abused substances?

How do neurotransmitters (e.g. dopamine, glutamate, GABA) and
brain energy utilization impact one another with and without exposure to abused
substances?

Are there brain metabolic differences during critical periods
(e.g. pre-natal, post-natal, adolescence) relevant to abused substances? Are
there differences in males and females? If so, what are the molecular
regulatory pathways involved?

How is regulation of brain energy utilization impacted by the
combination of chronic substance use, HIV infection, and antiretroviral
treatment?

What are the consequences of drug-induced energetic disruption on
neuroplastic processes (e.g. learning, memory, behavior and cognition)? To
what extent are any changes observed due to the effects of abused substances on
diet/nutrition (e.g. appetite suppression or enhancement)?

Are there differences in brain energy utilization in individuals
in pain versus those that are not in pain? Do prescription opioids alter brain
energy production or utilization differently in these individuals?

Are there genetic polymorphisms in nuclear or mitochondrial genes
relevant to brain energy utilization (e.g. lactate transporters) that may
influence substance abuse phenotypes?

What is the impact of substances of abuse on molecular regulation
of mitochondrial function or on nuclear/mitochondrial communication?

Does exposure to substances of abuse influence mitochondrial
biogenesis? Do these processes interact to impact dendritic spine formation in
brain areas relevant to substance abuse?

Do mitochondria in different brain cell types of relevance to
substance abuse have distinct molecular or structural phenotypes? Is there
variation in mitochondrial phenotypes related to the subcellular location of
the mitochondria? What molecular processes regulate these mitochondrial
differences?

To what extent do mitochondria differ in their ability to
metabolize drugs of abuse (e.g. via cytochrome P450 enzymes) to exacerbate or
ameliorate their effects?

What are the molecular regulatory mechanisms by which abused
substances induce oxidative stress in the mitochondria and deplete ATP in
neurons and glia? How is redox homeostasis in the brain altered by chronic
exposure to drugs of abuse?

Special Considerations

HIV/AIDS Counseling and Testing Policy for the National
Institute on Drug Abuse: In light of recent significant advances in rapid
testing for HIV and in effective treatments for HIV, NIDA has revised its 2001
policy on HIV counseling and testing. NIDA-funded researchers are strongly
encouraged to provide and/or refer research subjects to HIV risk reduction
education and education about the benefits of HIV treatment, counseling and
testing, referral to treatment, and other appropriate interventions to prevent
acquisition and transmission of HIV. This policy applies to all NIDA funded
research conducted domestically or internationally. For more information seehttp://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended
Guidelines for the Administration of Drugs to Human Subjects: The National
Advisory Council on Drug Abuse (NACDA) recognizes the importance of research
involving the administration of drugs with abuse potential, and dependence or
addiction liability, to human subjects. Potential applicants are encouraged
to obtain and review these recommendations of Council before submitting an application
that will administer compounds to human subjects. The guidelines are available
on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects

Data Harmonization for Substance Abuse and Addiction via the
PhenX Toolkit: NIDA strongly encourages investigators involved in
human-subjects studies to employ a common set of tools and resources that will
promote the collection of comparable data across studies and to do so by
incorporating the measures from the Core and Specialty collections, which are
available in the Substance Abuse and Addiction Collection of the PhenX Toolkit
(www.phenxtoolkit.org). Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html)
for further details.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or
both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH Policy
on Late Submission of Grant Applications states that failure to complete
registrations in advance of a due date is not a valid reason for a late
submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should
work with their organizational officials to either create a new account or to
affiliate an existing account with the applicant organization’s eRA Commons
account. If the PD/PI is also the organizational Signing Official, they must
have two distinct eRA Commons accounts, one for each role. Obtaining an eRA
Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some components
marked optional in the application package are required for submission of
applications for this FOA. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Letter

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Applicationsthat do not include exposure to a substance of abuse, that
focus solely on alcohol without investigating other abused substances of NIDA
relevance, or do not have a primary focus on molecular mechanisms regulating
brain energy utilization will NOT be considered responsive to this FOA. Applications
deemed by NIDA program staff to be non-responsive to this FOA will be
administratively withdrawn and will not be reviewed.

Appendix: Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the
status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by components of participating organizations,
NIH. Applications that are incomplete and/or nonresponsive will not be
reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field? Will the proposed study significantly improve our understanding of neuroplastic processes or the brain
effects of substances of abuse?”

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed? How well is substance abuse exposure (or withdrawal or reinstatement) incorporated into the
proposed work? How well does the application explore molecular regulation of
brain energy utilization?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the National Institute on Drug Abuse, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted
in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds
with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a
second level of review by the National Advisory Council on Drug Abuse. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to
the applicant organization for successful applications. The NoA signed by the
grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH Grants
Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.